Postoperative intravenous infusion of donor-derived transplant acceptance-inducing cells as an adjunct immunosuppressive therapy in a porcine pulmonary allograft model.
There is very limited published information testifying to the safety and possible complications of cell-based therapies. Accurately assessing the potential risks of translating novel, cell-based immunosuppressive protocols into clinical trials is therefore extremely difficult. This report describes the use of a pulmonary allograft model in outbred miniature pigs as a preliminary step in the development of a safe, clinically feasible, cell-based immunosuppressive protocol. Single lung transplants were performed in 22 MHC Class I-mismatched donor-recipient pairs, which were randomized between four treatment groups. For the first 28 days postoperatively, all animals were immunosuppressed with methylprednisilone and tacrolimus, with or without preoperative irradiation; subsequently, pharmacological immunosuppression was stopped in all treatment groups. Animals in two groups also received a central venous infusion of donor-derived 'transplant acceptance-inducing cells' (TAICs) on the seventh and 14th days postoperatively. Allograft survival was monitored by sequential chest X-rays, bronchoscopies and transbronchial biopsy histologies. No acute adverse events were associated with the administration of TAICs and there was no evidence of accelerated graft rejection. The observations presented in this report represent an important first step towards the development of a clinically applicable protocol for the use of TAIC therapy in lung transplantation.
Warnecke
Gregor
G
Division of Thoracic and Cardiovascular Surgery, Hannover Medical School, Hannover, Germany.
Hutchinson
James A
JA
Riquelme
Paloma
P
Kruse
Bianca
B
Thissen
Stefanie
S
Avsar
Murat
M
Zehle
Gregor
G
Steinkamp
Thomas
T
Peters
Carsten
C
Baumann
Rolf
R
Gövert
Felix
F
Ungefroren
Hendrik
H
Länger
Florian
F
Simon
André R
AR
Karstens
Johann H
JH
Kaever
Volkhard
V
Haverich
Axel
A
Fändrich
Fred
F
Strüber
Martin
M
D000208:Acute Disease; D000818:Animals; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D005938:Glucocorticoids / Q000494:pharmacology; D006084:Graft Rejection / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control / Q000628:therapy*; D006085:Graft Survival / Q000276:immunology; D016130:Immunophenotyping; D007165:Immunosuppression Therapy / Q000379:methods*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007262:Infusions, Intravenous; D016040:Lung Transplantation; D008264:Macrophages / Q000276:immunology; D008775:Methylprednisolone / Q000494:pharmacology; D011182:Postoperative Care; D013552:Swine; D013556:Swine, Miniature; D016559:Tacrolimus / Q000494:pharmacology; D018183:Transplantation Chimera; D014184:Transplantation, Homologous
D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D016559:Tacrolimus; D008775:Methylprednisolone